Aïcha Kante ^1,2,3 Mathieu F Chevalier ^2,4* Damien Sene ^2,3* Jeanne Chauffier ^2,3* Stephane Mouly ^3,5* Glenn Benjamin Chousterman ^6,7 Feriel Azibani ^6* Benjamin Terrier ^8,9* Theo Pezel ^10,6* Cloé Comarmond ^2,3*

• ¹ Université Paris Cité, Paris, Île-de-France, France
• ² INSERM U976 HIPI Human Immunology, Pathophysiology, Immunotherapy, Paris, France
• ³ Médecine Interne et Immunologie Clinique, Hôpital Lariboisière, Paris, France
• ⁴ Institut de Recherche Saint Louis, Université de Paris, Paris, France
• ⁵ INSERM U1144 Optimisation Thérapeutique en Neuropsychopharmacologie, Paris, Île-de-France, France
• ⁶ INSERM U942 Biomarqueurs Cardioneurovasculaires, Paris, Île-de-France, France
• ⁷ Service d'Anesthésie Réanimation, Hôpital Lariboisière, Paris, France
• ⁸ Service de Médecine Interne, Hôpital Cochin, Paris, France
• ⁹ INSERM U970 Paris Centre de Recherche Cardiovasculaire (PARCC), Paris, Île-de-France, France
• ¹⁰ Département de cardiologie, Hôpital Lariboisière, Paris, France

Auto-immune and inflammatory diseases are heterogenous in their clinical manifestations and prognosis, even among individuals presenting with the same pathology. Understanding the immunological alterations involved in their pathogenesis provides valuable insights in different clinical phenotypes and treatment responses. Immunophenotyping could lead to significant improvements in diagnosis, monitoring, initial treatment decisions and follow-up in autoimmune and inflammatory diseases. Mass cytometry provides measurement of over 40 simultaneous cellular parameters at single-cell resolution, and therefore holds immense potential to evaluate complex cellular systems and for high-dimensional single-cell analysis. The high dimensionality of mass cytometry provides better coverage of immune populations dynamics, with sufficient power to identify rare cell types compared to flow cytometry. In this comprehensive review, we explore how mass cytometry findings contributed in the past decade to a deeper understanding of the cellular actors involved in systemic auto-immune and auto-inflammatory diseases with their respective therapeutic and prognostic impact. We also delve into the bioinformatical approaches applied to mass cytometry to analyze the high volumes of data generated, as well as the impact of the use of complementary single cell RNA sequencing, and their spatial modalities. Our analysis highlights the fact that mass cytometry captures major information on cell populations providing insights on the complex pathogenesis of autoimmune diseases. Future research designs could include mass cytometry findings in association to other -omics to stratify patients in adequate therapeutic arms and provide advancements in personalized therapies in the field of auto-immune and inflammatory diseases.